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Mimicking a Good Thing

Released: Thursday, November 30, 2006

BATON ROUGE - A Louisiana native scientist has come home, bringing years of experience and a desire to “mimic” a good thing - eating less to be healthier and live longer.

Don Ingram, Ph.D., born and educated in Bogalusa, earned a psychology degree from LSU in 1970 before moving to Athens, Georgia, where he finished his Ph.D. in psychology and gerontology (the science of aging) at the University of Georgia. Since then, Ingram has made a career out of studying aging, especially the search for how to slow aging.

One new finding in which Ingram is most interested is the possibility that if humans eat less - a lot less - they may be healthier and live longer, avoiding many age-related ailments along the way. It is a growing field of research called calorie restriction. Laboratory experiments have clearly shown that animals whose diets are cut by up to 30-percent from normal levels are healthier and live longer.

The problem, according to Ingram, is that calorie restriction while avoiding malnutrition is big challenge for anyone. As we all seem to find out at one time or another, a lifetime of dieting is a long and arduous journey, one that most dieters find hard to stay on track. And when you’re trying to reduce calorie intake by a third below normal levels, well, “It’s going to be very, very difficult to follow that for a lifetime.”

For more than 26 years, Ingram worked out of the labs of the National Institute on Aging in Baltimore, Maryland, where he became the Chief of the Laboratory of Experimental Gerontology. Both are part of the National Institutes of Health (NIH).

His research at NIH specifically focused on nutritional and pharmacological interventions designed to slow the rate of aging and therefore reduce the risk of age-related disease and functional decline. His work eventually led to patented drugs for the treatment of Alzheimer’s disease, and now he’s working on a whole new idea.

Ingram is the latest senior researcher to join the faculty of the Pennington Biomedical Research Center alongside other experts in reduced-calorie research.

“The NIH has a very good set-up, great resources for research, but coming here was astounding. The Center is a remarkable place; wonderful work atmosphere, incredible and innovative research, and a fantastic physical facility,” said Ingram.

And that’s where Ingram hopes his idea will blossom. Combining his experience in aging, drug development, and calorie restriction, he wonders if a chemical compound, a nutrient, or drug, might cause the body to mimic calorie restriction and yield similar healthy results.

Ingram and his lab team have been fascinated by what happens in organisms when food supplies drop significantly, or as he puts it, the organisms get into a “very low energy” environment. Many organisms have a genetically programmed reaction: they slow down development, halt reproduction, reduce their metabolic rate, and some even go into a suspended animation or hibernation-like state. Yeast, worms, flies and rodents all exhibit this genetically controlled response to low energy availability. In addition, the same response mechanisms also turn on many biochemical defenses to enhance response to stress and ward off disease.

“If you’re going to stop growing and reproducing, you better have a way to survive,” Ingram said, “and these organisms have a number of genes that, when stimulated by low energy (food) intake, lead to a cascade of responses that eventually result in slowing many aging processes, and thus produce subsequently greater health with less disease and longer life.”

The question is, do humans have a similar set of genes or genetic responses that also slow down aging processes, ward off illness and contribute to longer life when food intake is severely reduced? Calorie restriction studies say, possibly, “yes,” but Ingram would like to know if the same response can be created with a chemical compound, whether a drug or nutrient.

Ingram and his colleagues have seen a “fake” glucose (sugar) molecule cause responses similar to calorie restriction but did not reduce food intake substantially. When the imposter glucose makes its way into cells, it prevents cells from being able to use available, real glucose. By making glucose unavailable to the cells, the imposter creates a situation that “mimics” a low-food or low-energy environment, which seems to set off events that lead to a biochemical slow-down and enhanced stress responses similar to actual calorie restriction.

Currently, the search is on for a compound that would create the beneficial effects of calorie restriction without the life-long dedication to severe diet restriction and without any harmful side-effects.

It is hard to say when or if that will occur, but if Dr. Ingram and his colleagues continue the successes they have achieved so far, calorie restriction mimicry could become a reality.

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The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the causes of obesity, diabetes, cardiovascular disease, cancer and dementia. Itis a campus of the Louisiana State University System and conducts basic, clinical and population research. The research enterprise at the Center includes approximately 80 faculty and more than 25 post-doctoral fellows who comprise a network of 50 laboratories supported by lab technicians, nurses, dieticians, and support personnel, and 19 highly specialized core service facilities. The Center's more than 500 employees perform research activities in state-of-the-art facilities on the 234-acre campus located in Baton Rouge, Louisiana.